I was based upon Study 1053 titled “A Pivotal Multicenter Trial ofMoxetumomab Pasudotox in Relapsed/Refractory Hairy Cell Leukemia”(NCT01829711). Study 1053was conducted in patients with histologically confirmed HCL or HCL variant with a need for therapybased on presence of cytopenias or splenomegaly and who had received prior treatment with at least 2systemic therapies, including 1 purine nucleoside analog (PNA).
Eligible patients had serum creatinine≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min as estimated by the Cockcroft Gault equation.
A total of 80 patients were enrolled; 77 with classic HCL and 3 with HCL variant. The median age was60 years (range: 34 to 84) years, 79% were male, and 94% were Caucasian. At baseline, 98% of patientshad an ECOG performance status of 0 or 1. The median number of prior treatments was 3 (range: 2 to11); all patients received prior PNA therapy, including 29% in combination with rituximab.
The mostcommon other prior treatment regimens were rituximab monotherapy (51%), interferon-alpha (25%), anda BRAF inhibitor (18%). At baseline, 33% (26/80) of patients had low hemoglobin (< 10 g/dL), 68%(54/80) of patients had neutropenia (< 1000/mm3), and 84% (67/80) patients had baseline platelet counts< 100,000/mm3. About 35% of patients had enlarged spleens (≥ 14 cm, assessed by BICR) at baseline.
Patients received LUMOXITI 0.04 mg/kg as an intravenous infusion over 30 minutes on Days 1, 3, and 5of each 28-day cycle for a maximum of 6 cycles or until documentation of complete response (CR),disease progression, or unacceptable toxicity. The median duration of follow-up was 16.7 months (range:2 to 49). An independent review committee (IRC) performed efficacy eva luations using blood, bonemarrow, and imaging criteria adapted from previous HCL studies and consensus guidelines.
Efficacy of LUMOXITI in HCL was eva luated by the IRC-assessed rate of durable CR, as confirmed bymaintenance of hematologic remission (hemoglobin ≥ 11 g/dL, neutrophils ≥ 1500/mm3, and platelets≥ 100,000/mm3 without transfusions or growth factor for at least 4 weeks) more than 180 days afterIRC-assessed CR. The IRC-assessed durable CR rate was 30% (24/80 patients; 95% CI: 20, 41).
Additional efficacy outcome measures included overall response rate (ORR), CR, and duration ofresponse (see Table 6).
Table 6: Additional Efficacy Results in Patients with HCL in Study 1053Independent Review Committee (IRC) Assessed
N=80
Overall Response Rate
Overall Response Rate* (%) [95% CI] 75 [64, 84]
Complete Response† (%) [95% CI] 41 [30, 53]
Partial Response‡ (%) [95% CI] 34 [24, 45]
Duration of Response
Median in months [range] NR [0+ to 43+]
Independent Review Committee (IRC) Assessed
N=80
Median in months [range] NR [0+ to 40+]
CI=Confidence Interval; NR=Not Reached; + indicates censored observations * ORR defined as best overall response of CR or PR.
† CR defined as clearing of the bone marrow of hairy cells by routine Hematoxylin & Eosin stain, radiologic resolution of preexistinglymphadenopathy and/or organomegaly, and hematologic remission. ‡ PR defined as ≥ 50% decrease or normalization (< 500/mm3) in peripheral blood lymphocyte count, reduction of pre-existing
lymphadenopathy and/or organomegaly, and hematologic remission.
The median time to ORR and CR was 5.7 months (range: 1.8 to 12.9) and 5.9 months (range 1.8 to 13.2),res |
